FS-1502 in <i>HER2</i>-positive advanced breast cancer: Results from an open-label, phase 1 study.
Authors: Qiao Li, Ying Cheng, Zhongsheng Tong, Yunjiang Liu, Xian Wang, Min Yan, Jianhua Chang, Shusen Wang, Caiwen Du, Liang Li, Chunjiao Wu, Mingxia Wang, Zhuo Wang, Zhuli Wu, Yongli Jin, Yongjiao Zhang, Ai-Min Hui, Xingli Wang, Binghe Xu
Journal: Journal of Clinical Oncology (2023)

3044 Background: FS-1502 is an anti-HER2 antibody-drug conjugate that was well tolerated and showed good antitumor activity in patients (pts) with advanced HER2 -expressing solid tumors in the dose-escalation stage of the current Phase 1 study. The results were presented at SABCS 2022. The recommend Phase 2 dose (RP2D) was 2.3 mg/kg IV once every 3 weeks. Here, we report the efficacy and safety of HER2-positive breast cancer (BC) pts treated with FS-1502 at the RP2D. Methods: This open-label Phase 1 trial was conducted at 9 hospitals in China. Heavily pretreated HER2-positive (IHC 3+ or 2+/FISH+) BC pts who had failed prior anti-HER2 therapy were recruited in the dose-expansion stage. All HER2-positive BC pts treated at the RP2D were pooled for analysis. Efficacy endpoints included objective response rate (ORR) and disease control rate (DCR) per RECIST v1.1. Safety endpoints included treatment-emergent adverse events (TEAEs) and the laboratory data. Results: As of cutoff date, December 24, 2022, the median study follow-up duration was 5.2 months. A total of 70 female HER2-positive BC pts, with a median age of 51.8 (range: 31-76) years, were enrolled and received at least one dose of FS-1502. The median prior therapy line was 3 (range: 1-16), and 91.4% (64/70) of pts had previously received at least 2 therapy lines. The most common metastasis organs were lung 55.7% (39/70), lymph node 54.3% (38/70) and bone 50% (35/70). 81.4% (57/70) of pts had at least 3 metastatic lesions. All pts had previously received anti-HER2 therapy, among which trastuzumab ± pertuzumab (n = 67, 96%) and pyrotinib (n = 52, 74%) were the most common. Among 68 efficacy-evaluable pts, the best ORR of 52.9% (36/68) (95% CI, 40.45-65.17) was achieved with 2 complete responses and 34 partial responses. DCR was 88.2% (60/68), median progression-free survival was 15.5 months (95% CI, 4.57,-), and median duration of response was 12.9 months (95% CI, 5.72,-). FS-1502 was well tolerated. No related interstitial lung disease occurred in any grade. Eye toxicity was mostly Grade 1 or 2 of dry eye and keratitis. Grade ≥ 3 study-related TEAEs were reported in 27 (38.6%) pts, in which the most common events (≥ 5%) were hypokalemia (18.6%), platelet count decreased (7.1%), and neutrophil count decreased (5.7%). One (1.4%) patient experienced adverse events leading to drug discontinuation (hemoptysis). Adverse events leading to death were reported in 2 (2.9%) pts (bacterial pneumonia and hemoptysis, respectively). Bacterial pneumonia was not related to FS-1502, while hemoptysis was possibly related to the drug. Conclusions: FS-1502 demonstrated very promising antitumor activity and was well tolerated in heavily pretreated HER2-positive BC, with mild eye toxicity and no related interstitial lung disease reported. A Phase 3 clinical trial is under planning to further confirm efficacy and safety of FS-1502 in pts with advanced HER2-positive BC. Clinical trial information: NCT03944499 .